A5058284896- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Electrolyte and hormonal disorders
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Cystic Fibrosis Research Advances
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Biomedical and Chemical Research
- Hormonal Regulation and Hypertension
- Magnesium in Health and Disease
- Neonatal Respiratory Health Research
- Neuroendocrine regulation and behavior
- Drug Transport and Resistance Mechanisms
- Genetic and Kidney Cyst Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Physics and Engineering Research Articles
- Medical and Health Sciences Research
- Retinal Development and Disorders
- Renal function and acid-base balance
- Economic and Social Issues
- Connexins and lens biology
- Adenosine and Purinergic Signaling
- Environmental Science and Technology
Friedrich-Alexander-Universität Erlangen-Nürnberg
2016-2025
Bayer (Germany)
2019-2024
Universitätsklinikum Erlangen
2016
Institute of Molecular Biotechnology
2007-2014
University of Oxford
1998-2007
Goethe University Frankfurt
1995-1997
Yale University
1992-1995
Freie Universität Berlin
1987-1991
Klinikum Görlitz
1989
Proteinuria and increased renal reabsorption of NaCl characterize the nephrotic syndrome. Here, we show that protein-rich urine from rats patients with syndrome activate epithelial sodium channel (ENaC) in cultured M-1 mouse collecting duct cells <i>Xenopus laevis</i> oocytes heterologously expressing ENaC. The activation depended on urinary serine protease activity. We identified plasmin as a by matrix-assisted laser desorption/ionization time of-flight mass spectrometry. Purified activated...
Aldosterone-induced serum- and glucocorticoid-inducible kinase isoform 1 (SGK1) contributes to the regulation of epithelial sodium channel (ENaC), activity which is critical for long term blood pressure control. SGK1 thought enhance ENaC surface expression by phosphorylating Nedd4-2 thereby preventing retrieval degradation. In outside-out membrane patches Xenopus laevis oocytes heterologously expressing ENaC, amiloride-sensitive currents were enhanced phosphatase inhibitors dependent on...
Proteases that cleave protease-activated receptor-2 (PAR(2)) at Arg(36)↓Ser(37) reveal a tethered ligand binds to the cleaved receptor. PAR(2) activates transient receptor potential (TRP) channels of nociceptive neurons induce neurogenic inflammation and pain. Although proteases non-canonical sites can trigger distinct signaling cascades, functional importance PAR(2)-biased agonism is uncertain. We investigated whether neutrophil elastase, biased agonist PAR(2), causes pain by activating...
Confluent M-1 mouse cortical collecting duct (CCD) cells express highly selective low-conductance amiloride-sensitive Na+ channels (B. Letz, A. Ackermann, C. M. Canessa, B. Rossier, and Korbmacher, J. Membr. Biol. 148: 129-143, 1995). Here we investigated the effect of forskolin on membrane voltage whole cell currents confluent using patch-clamp technique. Forskolin (1 microM) reduced hyperpolarization in response to amiloride (10 from 17 4 mV decreased inward 81 26 pA. Furthermore,...
ABSTRACT. Mineralocorticoids stimulate Na+ reabsorption and K+ secretion in principal cells of connecting tubule collecting duct. The involved ion channels are ENaC ROMK1, respectively. In Xenopus oocytes, the serum glucocorticoid-sensitive kinase SGK1 has been shown to increase activity by enhancing its abundance plasma membrane. With same method, ROMK1 appeared be insensitive regulation SGK1. On other hand, colocalize with NHERF2, a protein mediating targeting trafficking transport...
The mechanisms by which proteases activate the epithelial sodium channel (ENaC) are not yet fully understood. We investigated effect of extracellular on rat ENaC heterologously expressed in Xenopus laevi s oocytes. Application trypsin increased whole‐oocyte currents about 8‐fold without a concomitant increase surface expression. stimulatory was preserved oocytes expressing αγ‐ENaC, but abolished αβ‐ENaC. Thus, γ‐subunit appears to be essential for activation proteases. Site‐directed...
Aldosterone is thought to be the main hormone stimulate epithelial sodium channel (ENaC) in aldosterone-sensitive distal nephron (ASDN) comprising late convoluted tubule (DCT2), connecting (CNT) and entire collecting duct (CD). There immunohistochemical evidence for an axial gradient of ENaC expression along ASDN with highest DCT2 CNT. However, most our knowledge about renal function stems from studies cortical (CCD). Here we investigated transition zone DCT2/CNT or CNT/CCD microdissected...
Increased activity of the epithelial sodium channel (ENaC) in respiratory airways contributes to pathophysiology cystic fibrosis (CF), a genetic disease caused by mutations transmembrane conductance regulator (CFTR) gene. In some patients suffering from atypical CF mutation can be identified only one CFTR allele. We recently this group heterozygous (W493R) alpha-subunit ENaC. Here, we investigate functional effects expressing wild-type alpha beta gamma ENaC or mutant alpha(W493R)beta Xenopus...
Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice define renal control of homeostasis in complete deficiency. AS(-/-) were normokalemic and tolerated a physiologic dietary load (2% K(+), 2 days) without signs illness, except some degree polyuria. With supraphysiologic intake (5% K(+)), decompensated became hyperkalemic. High-K(+) diets induced upregulation the outer medullary channel mice, whereas epithelial sodium...
1 Using equivalent short circuit current (ISC) measurements we examined the effect of extracellular ATP on transepithelial ion transport in M-1 mouse cortical collecting duct cells. Apical addition produced a rapid transient peak increase ISC. This was followed by fall below basal ISC due to reduction amiloride-sensitive component. 2 The ATP-induced preserved presence apical amiloride while it reduced absence Cl− and channel blockers diphenylamine-2-carboxylic acid (DPC, mM), DIDS (300 μM)...
Apical nonselective cation channels with an average single-channel conductance of 34 +/- 2.3 pS were found in M-1 mouse cortical collecting duct cells. Channel activity is increased by depolarization and abolished cytoplasmic calcium removal. Cytoplasmic application 0.1 mM cGMP decreases channel open probability 27%. cDNAs corresponding to approximately 40% the coding region photoreceptor isolated polymerase chain reaction from cells a rat kidney cDNA library. The kidney-derived sequence...
The high level of ascorbic acid (AA) in the aqueous humor many mammals suggests an active transport AA across double-layered ciliary epithelium from blood to humor. We used [14C]AA study uptake bovine pigmented epithelial cells tissue culture. observed a 40-fold intracellular accumulation AA, which was dependent on extracellular Na+. With labeled dehydroascorbate (DHA, oxidized form vitamin) medium, there 20-fold label. However, time course DHA different compared with and not Na+ dependent,...
We investigated whether mutations in the genes that code for different subunits of amiloride-sensitive epithelial sodium channel (ENaC) might result cystic fibrosis (CF)-like disease. In a small fraction patients, disease could be potentially explained by an ENaC mutation Mendelian mechanism, such as p.V114I and p.F61L SCNN1A. More importantly, more than three-fold significant increase incidence several rare polymorphisms was found patient group (30% vs. 9% controls), indicating involvement...
The epithelial sodium channel (ENaC) is probably a heterotrimer with three well characterized subunits (alphabetagamma). In humans an additional delta-subunit (delta-hENaC) exists but little known about its function. Using the Xenopus laevis oocyte expression system, we compared functional properties of alphabetagamma- and deltabetagamma-hENaC investigated whether can be proteolytically activated. amiloride-sensitive ENaC whole-cell current (DeltaI(ami)) was 11-fold larger in oocytes...
Proteolytic processing of the amiloride-sensitive epithelial sodium channel (ENaC) by serine proteases is known to be important for activation. Inappropriate ENaC activation may contribute pathophysiology cystic fibrosis and could involved in retention pathogenesis arterial hypertension context renal disease. We hypothesized that addition proteases, cathepsin activate ENaC. Cathepsin belong group cysteine play a pathophysiological role inflammatory diseases. Under conditions, cathepsin-S...
Hypervolemia is a common feature of patients with CKD and associated hypertension. Recent work has shown stimulation sodium retention by urinary plasmin during nephrotic syndrome. However, it unclear whether plasminuria plays role in stable non-nephrotic proteinuria.In this cross-sectional study, we analyzed the fluid status 171 consecutively presenting to our outpatient clinic from 2012 2013 using bioimpedance spectroscopy (Body Composition Monitor [BCM]; Fresenius Medical Care, Germany)...
Using a mouse model with inducible nephron-specific mineralocorticoid receptor (MR) deficiency, we demonstrated that MR is not only critical for maintaining aldosterone-dependent ENaC activity in CNT/CCD but also aldosterone-independent DCT2/CNT. Furthermore, cells of this latter nephron segment express little 11β-HSD2, which probably allows glucocorticoids to stimulate MR, resulting This site-specific regulation has physiologically relevant implications renal sodium and potassium homeostasis.